Safety Study of Nebulized Sodium Nitroprusside in Adult Acute Lung Injury
Recruitment status was: Recruiting
Acute lung injury (ALI) is caused by a wide variety of conditions, but always characterized by hypoxia and non-cardiogenic pulmonary edema. Current treatment of ALI is supportive and treatment of the underlying cause. New therapies to treat severe ALI have not been shown to improve survival, and are limited by financial and logistical resources.
The investigators propose to investigate the role of inhaled sodium nitroprusside (iSNP) in ALI. Sodium nitroprusside (SNP) is a vasodilator. When inhaled, SNP may travel to areas of the lung participating in gas exchange, and cause the blood vessels surrounding these areas to enlarge. This may result in an increase of blood vessels to these areas of the lung, and improve oxygenation. Currently, iSNP has not been studied in the adult population. Therefore, this study is intended to find the safety profile of varying doses of iSNP.
Acute Lung Injury
Acute Respiratory Distress Syndrome
Drug: Sodium Nitroprusside
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1 Study: The Determination of the Maximum Tolerable Dosage of Nebulized Sodium Nitroprusside in Adult Acute Lung Injury|
- The maximum tolerable dosage of nebulized sodium nitroprusside. This will be determined by the 3 + 3 dose finding design. [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]Participants will be followed for the duration of the intervention of 45 min. . It is anticipated it will take up to 1 year to recruit the required number of participants to determine the maximum tolerable dose of nebulized sodium nitroprusside.
- The change in measures of oxygenation (PaO2,SaO2,oxygenation index) during iSNP administration. [ Time Frame: 0 min, 15 min, 30 min, and 45 min ] [ Designated as safety issue: No ]
- The change in heart rate (HR), mean blood pressure (MAP) during iSNP administration. [ Time Frame: 0 min, 15 min, 30 min, and 45 min ] [ Designated as safety issue: Yes ]
- The presence or absence of lactate, and/or methemoglobin. [ Time Frame: 0 min, 15 min, 30 min, and 45 min ] [ Designated as safety issue: Yes ]
|Study Start Date:||May 2012|
|Estimated Study Completion Date:||June 2013|
|Estimated Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
|Experimental: Nebulized sodium nitroprusside||
Drug: Sodium Nitroprusside
Each subject will receive one of five possible dosages of nebulized sodium nitroprusside. The dosage will be determined by the 3 + 3 dose escalation design. Only a maximum of six patients will be given a particular dosage. Arterial blood gases will be drawn at 0 min, 15 min, 30 min and 45 min during nebulized sodium nitroprusside administration. Vitals signs will be recorded every five minutes. No changes to ventilator settings or vasopressor dosage or fluid administration will be allowed.
Other Name: Nipride, Nitropress
Acute lung injury (ALI) is a syndrome characterized by acute hypoxemic respiratory failure with bilateral pulmonary infiltrates that are not attributed to left atrial hypertension. ALI is responsible for significant mortality and morbidity in the critically ill population.
Novel rescue therapies used to support oxygenation in severe ALI include inhaled nitric oxide and high frequency oscillatory ventilation; however, neither have been shown to reduce mortality and both are limited by logistical and financial challenges.
Inhaled sodium nitroprusside (iSNP) is a vasodilator which causes local vasodilation of pulmonary capillaries surrounding functional alveoli, resulting in improved oxygenation by redistributing pulmonary blood flow to areas with better ventilation-perfusion ratios. As iSNP can be administered by a low-cost nebulizer and is relatively inexpensive compared to other novel rescue therapies, this modality may be an alternative therapy for patients with severe hypoxemia. Two pediatric studies support the use of iSNP in ALI; however, iSNP has not been studied in the adult ALI population. To determine whether iSNP can improve oxygenation in adult ALI, the maximum tolerable dose (MTD) must first be determined.
Our study aims to determine the MTD of iSNP in adult ALI through an open-label, non-randomized, single centered, dose escalation study design, whereby subjects will receive iSNP for thirty minutes and have various physiologic variables recorded.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01619280
|Mount Sinai Hospital, University of Toronto|
|Toronto, Ontario, Canada, M5G 1X5|
|Principal Investigator:||Sangeeta Mehta, MD FRCPC||Department of Critical Care Medicine, University of Toronto|
|Principal Investigator:||Terence Ip, MD||Department of Critical Care Medicine, University of Toronto|